EXPRESSION AND FUNCTION OF MSP HOMOLOGUES IN T PALLIDUM

MSP 同源物在 T Pallidum 中的表达和功能

• 批准号: 6332444
• 负责人: GLABER ARTURO CENTURION-LARA
• 金额: $ 14.65万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6332444
• 关键词: Treponema pallidum; bacterial antigens; bacterial genetics; bacterial proteins; flow cytometry; genetic polymorphism; genetic strain; immunofluorescence technique; microorganism population study; polymerase chain reaction; pore forming protein; protein localization; protein structure function; syphilis

As primary syphilis resolves, most treponemes are cleared from the chancre. However, a few organisms escape the immune response to cause secondary syphilis and ultimately to establish chronic infection. May theories have been proposed to explain Treponema pallidum's capacity for immune evasion, yet none has convincing experimental support. Antigen variation is one of the most intriguing theories, but not candidate antigens have been identified until now. The recent identification of a polymorphic multicopy gene family in T. pallidum that encodes for proteins with predicated amino acid homology to the major sheath protein (msp) of Treponema denticola provides a family of likely candidates. We call these T. pallidum proteins the msp-homologues. The broad goal of this proposal is to determine the cellular location and the function of the msp-homologue proteins. The specific aims of the project are the following: 1. Determine whether msp-homologues are surface exposed antigens in T. pallidum Nichols strain. This aim will test the hypothesis that some of the msp-homologues are surface exposed in living organisms. 2. Determine whether msp-homologues are involved in cell attachment and function as porins. This aim will determine whether the msp-homologue family has a role in two well-recognized mechanisms of pathogenesis of bacterial infections. 3. Determine whether T. pallidum Nichols strain represents a colonal bacterial population or is comprised of subpopulations of treponemes. This aim will test the hypothesis that, like other spirochetes, T. pallidum strains contain subpopulations that express heterogeneous msp- homologues. 4. Determine whether the msp-homologues undergo antigen variation or phase variation. Antigenic variation is common other pathogenic treponemes and the msp-homologue gene family has characteristics highly suggestive of genetic recombination and reassortment. This aim will test the hypothesis that individual msp-homologues either change (antigenic variation) or are no longer expressed (phase variation) during the course of infection. The studies proposed in this application will define the role of the msp- homologues in immune evasion and in the pathogenesis of syphilis.

随着一期梅毒的消退，大多数密螺旋体从下疳中被清除。然而，一些生物体逃脱了免疫反应，导致二期梅毒并最终形成慢性感染。人们提出了一些理论来解释梅毒螺旋体的免疫逃避能力，但没有一个得到令人信服的实验支持。抗原变异是最有趣的理论之一，但迄今为止尚未确定候选抗原。最近在梅毒螺旋体中鉴定出一个多态性多拷贝基因家族，该家族编码与齿垢密螺旋体主要鞘蛋白（msp）具有推测氨基酸同源性的蛋白质，这提供了一个可能的候选家族。我们将这些梅毒螺旋体蛋白称为 msp-同源物。该提案的主要目标是确定 msp 同源蛋白的细胞位置和功能。该项目的具体目标如下： 1.确定msp同源物是否是梅毒螺旋体Nichols菌株中的表面暴露抗原。这一目标将检验以下假设：一些 msp 同系物暴露在活生物体的表面。 2. 确定 msp-同源物是否参与细胞附着并发挥孔蛋白的功能。这一目标将确定 msp 同源家族是否在两种公认的细菌感染发病机制中发挥作用。 3.确定梅毒螺旋体Nichols菌株是否代表结肠细菌群体或由密螺旋体亚群组成。这一目标将检验以下假设：与其他螺旋体一样，梅毒螺旋体菌株包含表达异质 msp 同源物的亚群。 4.确定msp同源物是否经历抗原变异或相变异。抗原变异是常见的其他致病性密螺旋体，并且 msp 同源基因家族具有高度暗示遗传重组和重配的特征。这一目标将检验以下假设：在感染过程中，各个 msp 同源物要么发生变化（抗原变异），要么不再表达（相变异）。本申请中提出的研究将确定msp-同源物在免疫逃避和梅毒发病机制中的作用。